CD4 ⁺ T Cells and the Proinflammatory Cytokines Gamma Interferon and Interleukin-6 Contribute to Alveolar Bone Loss in Mice

Abstract

In this study, we used a mouse model to examine the role of the adaptive immune response in alveolar bone loss induced by oral infection with the human gram-negative anaerobic bacteriumPorphyromonas gingivalis. Severe combined immunodeficient mice, which lack B and T lymphocytes, exhibited considerably less bone loss than did immunocompetent mice after oral infection, suggesting that lymphocytes contribute to this process. Bone loss after oral infection was decreased in mice deficient in major histocompatibility complex (MHC) class II-responsive CD4+ T cells, but no change in bone loss was observed in mice deficient in MHC class I-responsive CD8+ T cells or NK1+ T cells. Mice lacking the cytokine gamma interferon or interleukin-6 also demonstrated decreased bone loss. These results suggest that the adaptive immune response, and in particular CD4+ T cells and the proinflammatory cytokines that they secrete, are important effectors of bone loss consequent to P. gingivalis oral infection. The studies also reinforce the utility of the mouse oral infection model in dissecting the pathobiology of periodontal disease.

T cell knockout mice have diminished alveolar bone loss after oral infection with Porphyromonas gingivalis

“…In regards to alveolar bone loss, we have previously shown that deletion of CD4 þ T cells, but not of CD8 þ T cells, abrogates bone loss after bacterial infection [13]. Teng and colleagues have also shown alveolar bone loss attributable to CD4 þ T cells [14].…”

“…P. gingivalis induces secretion of these cytokines [25^27]. Knockout mice missing either IL-6 or IFG do not lose alveolar bone after oral infection with P. gingivalis, while genetically matched wild-type strains do lose bone [13].…”

“…Mice lacking CD4 þ T cells or these cytokines experience less bone loss after oral infection. In contrast, CD8 þ T cell de¢cient mice exhibit the same degree of bone loss as do their immune competent parent strains [13]. Others have also shown that activated T cells can increase the number of osteoclasts, pushing the balance of bone remodeling in the direction of net resorption of alveolar bone [14].…”

“…The T cell de¢cient mouse strains in our previous study were produced by targeted deletion of major histocompatibility complex (MHC) I or II, inhibiting maturation of CD8 þ or CD4 þ T cells, respectively [13,16]. Because MHC deletions may have other e¡ects in addition to those on T cell maturation [16], we wished to con¢rm our previous results in mice made T cell de¢cient by a more direct knockout.…”

Prevalence of the −295 T-to-C promoter polymorphism of the interleukin (IL)-16 gene in periodontitis

“…According to recent pathogenetic models genetic factors causing imbalances in pro-and anti-inflammatory cytokine production along with an ineffective immune response against bacterial invasion were suggested to increase the susceptibility for periodontitis [22]. Among others interleukin-16 was shown to be involved in the regulation of the expression of several proinflammatory cytokines by cells of the monocyte/macrophage system [16].…”